ArticleHaematologica2014
The PDK1 master kinase is over-expressed in acute myeloid leukemia and promotes PKC-mediated survival of leukemic blasts.
Article in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Fission yeast Pdk1 kinase regulates cytokinesis and eisosomes.Molecular biology of the cell · 2025Article
- Fission yeast Pdk1 kinase regulates cytokinesis and eisosomes.bioRxiv : the preprint server for biology · 2025Article
- Integrative alternative splicing analysis reveals new prognosis signature in B-cell acute lymphoblastic leukemia.International journal of biological sciences · 2024Article
- Protein profiling by reverse phase protein array (RPPA) in classical hairy cell leukemia (HCL) and HCL-variant.EJHaem · 2022Article
- Article
- A cuproptosis-related genes signature associated with prognosis and immune cell infiltration in osteosarcoma.Frontiers in oncology · 2022Article
- Deciphering Metabolic Adaptability of Leukemic Stem Cells.Frontiers in oncology · 2022Review
- Phosphoinositide-Dependent Protein Kinases Regulate Cell Cycle Progression Through the SAD Kinase Cdr2 in Fission Yeast.Frontiers in microbiology · 2021Article
- Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival.Journal of cellular and molecular medicine · 2020Article
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- The Novel Phospholipid Mimetic KPC34 Is Highly Active Against Acute Myeloid Leukemia with Activated Protein Kinase C.Translational oncology · 2020Article
- Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma.Aging · 2020Article
- Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia.Cancer gene therapy · 2020Article
- Expression of PDK1 in malignant pheochromocytoma as a new promising potential therapeutic target.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Article
- Article
- Targeting PDK1 for Chemosensitization of Cancer Cells.Cancers · 2017Review
- Review
- MicroRNA-379 suppresses osteosarcoma progression by targeting PDK1.Journal of cellular and molecular medicine · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
PDK1 is a master kinase that activates at least six protein kinase groups including AKT, PKC and S6K and is a potential target in the treatment of a range of malignancies. Here we show overexpression of PDK1 in over 40% of myelomonocytic acute leukemia patients. Overexpression of PDK1 occurred uniformly throughout the leukemic population, including putative leukemia-initiating cells. Clinical outcome analysis revealed PDK1 overexpression was associated with poorer treatment outcome. Primary acute myeloid leukemia blasts over-expressing PDK1 showed improved in vitro survival and ectopic expression of PDK1 promoted the survival of myeloid cell lines. Analysis of PDK1 target kinases revealed that PDK1 overexpression was most closely associated with increased phosphorylation of PKC isoenzymes and inhibition of PKC strongly inhibited the survival advantage of PDK1 over-expressing cells. Membrane localization studies implicated PKCα as a major target for PDK1 in this disease. PDK1 over-expressing blasts showed differential sensitivity to PDK1 inhibition (in the low micromolar range) suggesting oncogene addiction, whilst normal bone marrow progenitors were refractory to PDK1 inhibition at effective inhibitor concentrations. PDK1 inhibition also targeted subpopulations of leukemic blasts with a putative leukemia-initiating cell phenotype. Together these data show that overexpression of PDK1 is common in acute myelomonocytic leukemia and is associated with poorer treatment outcome, probably arising from the cytoprotective function of PDK1. We also show that therapeutic targeting of PDK1 has the potential to be both an effective and selective treatment for these patients, and is also compatible with current treatment regimes.
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